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1 General Clinical Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Duke University School of Medicine, Durham, NC, USA
2 Department of Pharmaceutics, University of Washington, Seattle, WA, USA
3 Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA
4 General Clinical Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA
* To whom correspondence should be addressed. E-mail: pbwatkins{at}med.unc.edu.
A single nucleotide polymorphism (A6986G) in the cytochrome P450 3A5 (CYP3A5) gene distinguishes an expressor (*1) and a reduced-expressor (*3) allele and largely predicts CYP3A5 content in liver and intestine. CYP3A5 is the prevailing CYP3A isoform in kidney. We report that among renal microsomes from 21 organ donors, those from *1/*3 individuals had at least 8-fold higher mean kidney microsomal CYP3A5 content and 18-fold higher mean CYP3A catalytic activity than did those from *3/*3 individuals (p=0.0001 and p=0.0137, respectively). We also report significant associations between the A6986G polymorphism and systolic blood pressure (p=0.0007), mean arterial pressure (p=0.0075), and creatinine clearance (p=0.0035) among 25 healthy African-American adults. These associations remained significant when sex, age, and body mass index were taken into account. The mean systolic blood pressure of homozygous CYP3A5 expressors (*1/*1) exceeded that of homozygous non-expressors (*3/*3) by 19.3 mmHg. We speculate whether a high CYP3A5 expressor allele frequency among African-Americans may contribute to a high prevalence of sodium-sensitive hypertension in this population.
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